Kenneth J. DeLay

Modifying Risk Factors in the Management of Erectile Dysfunction: A Review

Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patients overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process.

Device Survival after Primary Implantation of an Artificial Urinary Sphincter for Male Stress Urinary Incontinence

Purpose: The AMS 800™ artificial urinary sphincter remains the gold standard for the surgical management of male stress urinary incontinence. We reviewed artificial urinary sphincter device survival after primary implantation. Materials and Methods: Retrospective data were collected from the AMS 800 patient information form database. Since 1972, 77,512 patient information forms for primary artificial urinary sphincter implantation have been completed in the United States. Following exclusion of procedures performed in children and females, and those labeled with an unknown surgical technique, 27,096 artificial urinary sphincter cases were included in the analysis. Collected variables included patient age, surgical approach, number of cuffs and surgeon volume. Measured outcomes included device explantation, device revision, component revision and time to each event. Results: Artificial urinary sphincter insertion was performed by low volume implanters in 22,165 (82.6%) cases. The approach was perineal in 18,373 cases (67.8%) and a tandem cuff was used in 2,224 cases (8.2%). Overall 5,723 cases required revision or explantation (21.1%). Younger age and penoscrotal approach were associated with higher device explantation and revision rates, while the use of a tandem cuff was associated with higher explantation rates. On multivariate analysis younger age, penoscrotal approach and use of a tandem cuff but not surgeon volume were significant factors associated with device explantation and component revision. Conclusions: These data provide a general overview of artificial urinary sphincter device survival and may serve urologists when counseling patients. Younger age, penoscrotal approach and use of a tandem cuff may be associated with inferior outcomes.

Review of Management Options for Patients With Atypical Peyronie's Disease

INTRODUCTION Peyronies disease (PD) is a wound-healing disorder of the tunica albuginea often associated with penile deformity. Less commonly, patients with PD might display atypical presentations such as ventral curvature, hourglass deformity, significantly shortened penis, and/or multiplanar curvature. AIM To review the available literature on the prevalence of and management options for atypical PD. METHODS A literature review was performed through PubMed from 1982 through 2016 regarding atypical PD. Keywords used for the search were Peyronies disease, atypical Peyronies disease, ventral Peyronies disease, ventral plaque, hourglass deformity, penile indentation, penile notching, short penis, shortened penis, shrunken penis, biplanar curvature, and multiplanar curvature. MAIN OUTCOME MEASURES To assess the various surgical and non-surgical techniques used for the management of atypical PD. RESULTS Collagenase Clostridium histolyticum is contraindicated for patients with ventral plaques and/or hourglass deformities. Patients with maintained erectile function and ventral PD plaques are best treated with intralesional injections of interferon alpha-2b or tunica plication. Patients with maintained erectile function with PD associated with hourglass deformity and/or multiplanar curvature are best treated with plaque incision or partial excision and grafting. Patients with a shortened penis could attempt conservative measures such as penile traction therapy and medical management. When erectile function is compromised, insertion of an inflatable penile prosthesis with or without ancillary straightening procedures should be recommended. Lengthening procedures can be attempted in very special circumstances by expert surgeons. CONCLUSION There is a paucity of data regarding atypical PD. Ventral plaques can be treated with intralesional injections or surgery, hourglass deformity and multiplanar curvatures are best managed surgically, and a shortened penis should be treated with non-invasive approaches. When concomitant erectile dysfunction is present, insertion of an inflatable penile prosthesis is recommended. Caution should be advised before undergoing ancillary penile lengthening maneuvers owing to the potential for serious complications. Yafi FA, Hatzichristodoulou G, DeLay KJ, Hellstrom WJG. Review of Management Options for Patients With Atypical Peyronies Disease. Sex Med Rev 2017;5:211-221.

Impact of Number of Cycles of Collagenase Clostridium Histolyticum on Outcomes in Patients With Peyronie's Disease

OBJECTIVE To analyze the impact of the number of cycles of collagenase Clostridium histolyticum (CCH) intralesional injection therapy on outcomes to further characterize CCH therapy. METHODS We conducted a retrospective review of the records of all patients treated with CCH for Peyronie disease between April 2014 and March 2016. Collected variables included demographics, pre- and posttreatment sexual function, penile curvature, penile vascular findings, and treatment outcomes. RESULTS A total of 77 patients were included in the study, of which 41 (53%) completed 4 cycles of treatment, consisting of 8 total injections. For all-comers regardless of numbers of cycles, curvature improved from 58.2° (standard deviation = 17.9°, range = 30°-105°) pre-treatment to 41.0° (standard deviation = 17.0°, range = 0°-85°) posttreatment (P < .001). In a repeated measures model, penile curvature improved significantly following the first 3 cycles, but not the fourth. Patients who had a ≥20% final reduction in curvature had a significantly greater change in curvature following the first injection (-16.2° vs -5.8°, P < .001). CONCLUSION Intralesional CCH therapy is an effective minimally invasive treatment for Peyronie disease, although the therapeutic benefit may decline after the third cycle of treatment. Patients with ≥20% reduction in curvature at the conclusion of treatment documented a greater curvature improvement after the first cycle and received more cycles of CCH.

Testosterone and the Prostate: Artifacts and Truths

Despite a lack of evidence, there have been stated concerns that testosterone replacement therapy (TRT) can pose a risk to men suffering with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). TRT may improve components of the metabolic syndrome, which is associated with worsening LUTS. Furthermore, the evidence suggests that TRT may decrease prostatic inflammation, which is also associated with worsening LUTS. The data on the relationship between TRT and LUTS have never shown worsening of LUTS, often show no change in LUTS, and occasionally show improvement.

Collagenase Clostridium histolyticum in the treatment of Peyronie’s disease: patient selection and perspectives

The safety and efficacy of the use of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie’s disease has been confirmed over the past several years. However, identification of the ideal patient population for use of this treatment is not well established. Multiple studies have attempted to delineate various patient-specific factors that may predict response to treatment with CCH, with the intent of enhancing patient selection. To date, these include baseline curvature severity, duration of disease, disease phase at presentation, plaque calcification, baseline erectile function, plaque size, age, comorbid diabetes, previous penile trauma, responsiveness to first treatment cycle, baseline penile shortening or pain, prior treatment with intralesional injection, compliance with plaque modeling, and atypical curvature. In addition, other studies have sought to explore various aspects of treatment with CCH that may affect patient perspective of treatment. They have focused on patient-reported outcomes, female partner considerations, cost of treatment, and potential confounders of patient satisfaction. This review provides a summary and analysis of currently available literature on topics of patient selection and perspectives in regard to treatment of Peyronie’s disease with CCH.

Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders, the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells (SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.

Pioglitazone’s beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n  = 7). The third group received BCNI and Pio treatment (BCNI  +  Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI  +  Pio  +  JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rβ (p-IGF-1Rβ), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI  +  Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI  +  Pio  +  JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rβ was observed in the BCNI  +  Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI  +  Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rβ. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

Successful Treatment of Residual Curvature in Peyronie Disease in Men Previously Treated With Intralesional Collagenase Clostridium Histolyticum

OBJECTIVE To determine the success and feasibility of surgically correcting residual curvature after intralesional collagenase clostridium histolyticum (CCH) for the treatment of Peyronie disease (PD). METHODS We performed a retrospective analysis of patients who had intralesional CCH treatment for PD and who subsequently underwent penile plication (PP), plaque incision and grafting (PIG), or inflatable penile prosthesis (IPP) placement. RESULTS Ten men who underwent PP, PIG, or IPP for the treatment of residual curvature after intralesional CCH were identified. Six patients underwent PP; 1 patient underwent PIG; and 3 patients underwent IPP with ancillary straightening maneuvers. The mean time from the last CCH injection to surgical correction was 150.9 days, or 5 months. The mean pre-CCH curvature was 67 degrees and the mean post-CCH curvature was 51 degrees. Eight of 10 patients had no residual curvature after surgical treatment. The mean postprocedure curvature was 4.5 degrees. The mean operative time was 72.1 minutes. The mean estimated blood loss was 20 mL. Increased fibrosis with increased surgical difficulty was noted in 3 (all <6 months post CCH treatment) of 10 patients. No postoperative complications were noted. CONCLUSION The surgical treatment of PD after intralesional CCH is safe and effective. If surgery is considered, this should be performed at least 6 months after the last CCH injection, given the potential for an increased inflammatory reaction in this area.

Practice Patterns in the Diagnosis and Management of Hypogonadism: A Survey of Sexual Medicine Society of North America Members

OBJECTIVE To describe practice patterns in the diagnosis and treatment of hypogonadism, as the optimal approaches are controversial. Multiple therapeutic options are currently available for hypogonadal men and treatment patterns vary considerably. The safety of testosterone therapy (TTh) remains understudied. MATERIALS AND METHODS A 23-question survey regarding diagnosis and treatment of hypogonadism was sent to all members of the Sexual Medicine Society of North America. Subgroup analyses compared responses between sexual medicine fellows and non-fellows, as well as between academic and nonacademic physicians, using a chi-squared analysis. RESULTS A total of 101 responses were included for analysis. The most common cutoff value used to diagnose hypogonadism was 300 ng/dL (55%, range = 200-400 ng/dL), and 31% felt comfortable giving TTh to a symptomatic patient with normal serum testosterone levels. No respondents felt that TTh increased a cardiovascular event risk. Of those surveyed, 68% would prescribe TTh to a hypogonadal man with severe lower urinary tract symptoms, and 64% would offer TTh to a man with low-risk prostate cancer on active surveillance. Fellowship-trained physicians were more likely to prescribe TTh to a man with hypogonadism but normal serum testosterone (P = .038), but they differed in the types of therapy they would use for men with hypogonadism who wish to preserve or regain fertility. CONCLUSION Significant variety exists in the diagnosis and treatment of hypogonadism. The majority of physicians will only prescribe TTh in the setting of subnormal serum testosterone levels, despite the presence of symptoms. None of the surveyed physicians reported concern over the risk of cardiovascular events.